A Study to Test the Safety of Three Experimental HIV Vaccines

There are currently several Phase I and II clinical trials being performed within AVEG to evaluate different HIV-1 vaccine candidates. The HIV-1 vaccination approach that is furthest along the clinical development pathway is the so-called prime-boost regimen of live recombinant canarypox priming (ALVAC-HIV vCP205) with recombinant subunit protein boosting (HIV-1 SF-2 rgp120 in MF59 adjuvant). The protein boost enhances neutralizing antibody responses against laboratory strains of HIV-1 in assays performed in vitro, as well as enhancing CD4 cell response and increasing the frequency of CD8 cytotoxic T lymphocytes (CTLs). In all of the ALVAC-HIV trials of the prime-boost regimen completed to date, the protein boost has been the HIV-1 SF-2 rgp120 subunit protein. This study is designed to explore whether boosting of live recombinant canarypox vaccination with a novel protein subunit, recombinant HIV-1 SF-2 p24, can enhance the CD4 and CD8 cell responses directed against HIV-1 antigens.

Volunteers are randomized to 1 of 5 groups. All volunteers receive a total of 4 immunizations, administered at Months 0, 1, 3, and 6. Each group receives a different combination of vaccines as follows:

Group 1: ALVAC-HIV vCP205 plus HIV-1 SF-2 p24. Group 2: ALVAC-HIV vCP205 plus MF59 adjuvant and citrate vehicle (control for HIV-1 SF-2 p24 and HIV-1 SF-2 rgp120) at Months 0 and 1; then ALVAC-HIV vCP205 plus HIV-1 SF-2 p24 at months 3 and 6.

Group 3: ALVAC-HIV vCP205 plus control at Months 0 and 1; then ALVAC-HIV vCP205 plus HIV-1 SF-2 p24 combined with HIV-1 SF-2 rgp120 at Months 3 and 6.

Group 4: ALVAC-HIV vCP205 plus control at Months 0 and 1; then ALVAC-HIV vCP205 plus HIV-1 SF-2 rgp 120 at Months 3 and 6.

Group 5: ALVAC-RG vCP65 (control for ALVAC-HIV vCP205) plus control at Months 0,1,3, and 6.

The study lasts for approximately 18 months; patients receive clinical evaluations to measure vaccine safety at 11 study visits at specified time intervals.

Inclusion criteria

You may be eligible for this study if you:

• Are between the ages of 18 and 60.
• Are HIV-negative.
• Are negative for Hepatitis B.
• Have a normal physical exam.
• Are available for 18 months of follow-up.
• Agree to use an effective method of birth control for 1 month before receiving a vaccine and during the study.

Exclusion criteria

You will not be eligible for this study if you:

• Have a history of an immunodeficiency, chronic illness, or cancer.
• Have a medical or psychiatric condition which would make you unable to comply with the study.
• Are at higher-risk for HIV infection; for example, have a history of injection drug use in the past year or practice higher risk sexual behavior.
• Have syphilis or tuberculosis.
• Have received a live vaccine in the past 60 days, have ever received an HIV vaccine or placebo in a previous HIV vaccine study, or have ever received a rabies vaccine.
• Have a history of a serious allergic reaction to a vaccine or to any other substance, including neomycin or egg products.
• Have received certain medications.
• Are pregnant or breast-feeding.